Novel strong interactions in the electroweak bosonic sector are expected to induce effective interactions between the Higgs doublet field and the electroweak gauge bosons which lead to anomalous W W Z and W W y vertices once the Higgs field acquires a vacuum expectation value. Using a linear realization of the Goldstone bosons, we consider a complete set of dimension-six operators which are SU(2)xU(l) gauge invariant and conserve C and P. This approach allows us to study effects of new physics which originates above 1 TeV and the Higgs boson mass dependence of the results can be investigated. Four of the dimension-six operators affect low energy and present CERN LEP experiments at the tree level. Another five influence neutral and charged current experiments at the one-loop level and three of these lead to anomalous W W Z and W W y vertices. Their loop contributions are at most logarithmically divergent, and these logarithmic divergences can be understood as renormalizations of the four operators which contribute at the tree level. Constraints on the remaining five operators can be obtained if one assumes the absence of cancellations between the tree level and one-loop contributions. The resulting bounds on anomalous triple gauge boson couplings are modest, which emphasizes the importance of direct measurements of the triple gauge boson vertices, e.g., in W + Wproduction at LEP 11. PACS number(s): 12.15. Cc, 12.15.Ji, 12.50.Lr, 14.80.Er

Of 150 clinical isolates of Neisseria gonorrhoeae recovered in 2001, we examined 55 clinical isolates of N. gonorrhoeae for which cefixime MICs were >0.125 g/ml and randomly selected 15 isolates for which cefixime MICs were <0.06 g/ml for analysis of alterations in the penicillin-binding protein 2 (PBP 2) gene. We found insertion of an extra codon (Asp-345a) in the transpeptidase domain of PBP 2, and this insertion occurred alone or in conjunction with other amino acid substitutions. We also found a mosaic PBP 2 that was composed of fragments of the PBP 2 proteins from Neisseria cinera and Neisseria perflava. This mosaic PBP 2 was significantly associated with decreased susceptibilities to penicillin and cephalosporins, especially oral cephalosporins. For most of the isolates with a mosaic PBP 2, the cefixime MICs were >0.5 g/ml and the cefdinir MICs were >1 g/ml. Analysis of chromosomal DNA restriction patterns by pulsed-field gel electrophoresis revealed that most isolates with the mosaic PBP 2 were genetically similar. The recombination events that generated the mosaic PBP 2 would likely have contributed to the decreased sensitivities to cephalosporins. Isolates with the mosaic PBP 2 appear to threaten the efficacy of the currently recommended regimen with cefixime. The emergence of such strains may be the result of the in vivo generation of clones in which interspecies recombination occurred between the penA genes of N. gonorrhoeae and commensal Neisseria species.

OBJECTIVES To compare the efficacy of two α1‐adrenoceptor antagonists, α1A‐adrenoceptor‐selective tamsulosin hydrochloride and α1D‐adrenoceptor‐selective naftopidil, in the treatment of lower urinary tract symptoms (LUTS) with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS Thirty‐four patients (mean age 72.4 years, sd 4.3, range 66–79) with LUTS (International Prostate Symptom Score, IPSS >8) secondary to BPH were enrolled in a randomized crossover study. Seventeen patients were initially prescribed naftopidil 50 mg for 4 weeks, followed by tamsulosin 0.2 mg for 4 weeks (group A); another 17 were initially prescribed tamsulosin 0.2 mg, followed by naftopidil 50 mg (group B). Patients changed to the alternative treatment after a 1‐week washout period. Efficacy criteria were improvement in LUTS (IPSS), quality of life (QoL), uroflowmetry, and pressure‐flow study (PFS) values based on the treatment with each agent. RESULTS At baseline there were no significant differences between the groups in IPSS, QoL, uroflowmetry values or PFS values, except for the volume at maximum desire to void. After treatment with each agent, the IPSS and QoL were significantly improved and the reduction in bladder outlet obstruction confirmed by PFS. Naftopidil was significantly more effective than tamsulosin in relieving nocturia. The increases from baseline (before treatment) to the endpoint (after treatment with each agent) in the volume at first desire and maximum desire to void were significantly higher with naftopidil than with tamsulosin. Involuntary contractions disappeared in two patients with relief of nocturia with naftopidil, but not with tamsulosin. The decrease in other symptoms of the IPSS, QoL, increase in uroflowmetry values and changes in other PFS values were similar for both agents. CONCLUSIONS The two agents provided similar efficacy in the treatment of LUTS with BPH. However, naftopidil was better than tamsulosin for nocturia. The disappearance of involuntary contraction and the greater increase in first‐desire volume with naftopidil may be associated with the relief of nocturia. The α1D‐adrenoceptor antagonist is effective in alleviating both voiding and storage symptoms. The α1D‐adrenoceptor antagonist may be more effective than the α1A‐adrenoceptor antagonist in LUTS with BPH.

ObjectiveThe objective of this study was to identify new causes of Charcot–Marie–Tooth (CMT) disease in patients with autosomal‐recessive (AR) CMT.MethodsTo efficiently identify novel causative genes for AR‐CMT, we analyzed 303 unrelated Japanese patients with CMT using whole‐exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation.ResultsWe identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta‐amyloid (Aβ)‐degrading enzymes. All patients had a similar phenotype consistent with late‐onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss‐of‐function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Aβ in Pittsburgh compound‐B positron emission tomography imaging.InterpretationOur results indicate that loss‐of‐function MME mutations are the most frequent cause of adult‐onset AR‐CMT2 in Japan, and we propose that this new disease should be termed AR‐CMT2T. A loss‐of‐function MME mutation did not cause early‐onset Alzheimer's disease. Identifying the MME mutation responsible for AR‐CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT. Ann Neurol 2016;79:659–672